Engineered nanomaterials (ENMs), including metal oxide and chalcogenide nanoparticles (NPs) are used in numerous applications. Specific chemical and physical properties of ENMs can induce various cellular responses, e.g. cellular uptake and distribution, which can subsequently lead to a variety of immunomodulatory responses. The increased use of metal oxide and chalcogenide ENMs has raised concerns about potential risks to the health of workers in industry and the general population. Inhalation exposure of NPs such as copper oxide (CuO) and cadmium sulfide (CdS) lead to pulmonary inflammation and increased production of multiple inflammatory cytokines. It has been shown that various NPs may affect dendritic cells functions. Despite new studies investigating the toxicity of metallic ENMs, immunomodulatory effects of these ENMs on innate and adaptive immunity are poorly understood. This administrative NHIR supplement proposes to establish a new collaboration of our team with Dr. Jon Houtman, Associate Professor of Immunology. He will guide us in the elucidation of adverse outcome pathways where complex innate and adaptive immune signaling and regulation are key events. We have recently developed an experimental house dust mite vaccine that is effective at protecting against dust mite allergen-induced allergic responses. We are using this allergy and vaccine model as a tool to investigate the effects of inhalation exposure of ENMs on the efficacy of the vaccine protecting against house dust mite allergy. Using this model in connection with CuO and CdS as model ENM exposures, we will deepen our understanding of potential immunomodulatory effects of ENMs in target and non-target organs after inhalation exposure.
This project seeks to elucidate adverse outcome pathways from molecular initiating events to whole animal effects following inhalation of engineered nanomaterials (ENMs) supplied by the Nanomaterials Health Implications Research Consortium's Engineered Nanomaterials Resource and Coordination Core. With a focus on immunomodulatory effects of ENMs, this supplement brings in an immunologist as a new collaborator to provide additional expertise to our project team. Specific aims include, a) investigate the effects of inhaled metal oxide and chalcogenide ENMs on the efficacy of a novel vaccine against house dust mite allergen, and b) characterize the immune cells upregulated and downregulated when vaccinated mice are exposed to inhaled metal oxide and chalcogenide ENMs.
| Morris, Angie S; Sebag, Sara C; Paschke, John D et al. (2017) Cationic CaMKII Inhibiting Nanoparticles Prevent Allergic Asthma. Mol Pharm 14:2166-2175 |
